Адреномедуллин – биологический маркер сердечной недостаточности: обзор современной литературы

Алиева А.М., Теплова Н.В., Воронкова К.В., Пинчук Т.В., Валиев Р.К., Шнахова Л.М., Рахаев А.М., Никитин И.Г. Адреномедуллин – биологический маркер сердечной недостаточности: обзор современной литературы. CardioСоматика. 2022;13(1):64–69. DOI: 10.17816/22217185.2022.1.201472

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Alieva AM, Teplova NV, Voronkova KV, Pinchuk TV, Valiev RK, Shnakhova LM, Rahaev AM, Nikitin IG. Adrenomedullin is a biological marker of heart failure: review of modern literature. Cardiosomatics. 2022;13(1):64–69.
DOI: 10.17816/22217185.2022.1.201472

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Аннотация

Доказано, что у пациентов с сердечной недостаточностью (СН) имеется повышенное содержание адреномедуллина (ADM) в плазме крови. Уровень биомаркера коррелирует со степенью тяжести гемодинамической дисфункции, а также с нейрогуморальными показателями, которые активируются в зависимости от степени тяжести застойной недостаточности кровообращения. Кроме того, экспрессия гена ADM в сердце и почках увеличивается при экспериментальной и клинической СН. В небольшом числе исследований изучали влияние инфузии ADM на гемодинамические показатели. Эти исследования в целом показали, что инфузия гормона имеет благоприятные гемодинамические эффекты и способствует поддержанию/улучшению функции почек, однако большинство испытаний были непродолжительными. Имеющиеся результаты предполагают, что повышение содержания ADM уменьшает негативное влияние вазоконстрикции и задержки натрия. Лучшее понимание роли биологического маркера при застойной недостаточности кровообращения может привести к разработке лекарственных препаратов, воздействующих на рецепторы ADM.

Ключевые слова: адреномедуллин, биологический маркер, сердечная недостаточность

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It has been proven that in patients with heart failure (HF), there is an increased level of adrenomedullin (ADM) in plasma. Biomarker indices correlate with the severity of hemodynamic dysfunction, as well as with neurohumoral indices, which are activated depending on the severity of congestive circulatory failure. In addition, the expression of the ADM gene in the heart and kidneys is increased in experimental and clinical HF. A small number of studies have examined the effect of ADM infusion. These studies have generally shown that hormone infusion has beneficial hemodynamic effects and promotes the maintenance/improvement of renal function, but most of the studies have been short-lived. The available results suggest that increasing ADM levels reduce the negative effects of vasoconstriction and sodium retention. A better understanding of the role of a biological marker in congestive circulatory failure may lead to the development of drugs that target ADM receptors.

Keywords: adrenomedullin, biological marker, heart failure

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Список литературы

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12. Schönauer R, Els-Heindl S, Beck-Sickinger AG. Adrenomedullin – new perspectives of a potent peptide hormone. J Pept Sci. 2017;23(7-8):472-85. DOI:10.1002/psc.2953
13. Dschietzig T, Azad HA, Asswad L, et al. The adrenomedullin receptor acts as clearance receptor in pulmonary circulation. Biochem Biophys Res Commun. 2002;294(2):315-8. DOI:10.1016/S0006-291X(02)00474-6
14. Holmes D, Corr M, Thomas G, et al. Protective effects of intermedin/adrenomedullin-2 in a cellular model of human pulmonary arterial hypertension. Peptides. 2020;126:170267. DOI:10.1016/j.peptides.2020.170267
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19. Maisel A, Mueller C, Nowak R, et al. Mid-region pro-hormone markers for diagnosis and prognosis in acute dyspnea: results from the BACH (Biomarkers in Acute Heart Failure) trial. J Am Coll Cardiol. 2010;19:2062‑76. DOI:10.1016/j.jacc.2010.02.025
20. Weber J, Sachse J, Bergmann S, et al. Sandwich immunoassay for bioactive plasma adrenomedullin. J Appl Lab Med. 2017;2(2):222-33. DOI:10.1373/jalm.2017.023655
21. Self WH, Storrow AB, Hartmann O, et al. Plasma bioactive adrenomedullin as a prognostic biomarker in acute heart failure. Am J Emerg Med. 2016;34(2):257-62. DOI:10.1016/j.ajem.2015.10.033
22. Tolppanen H, Rivas-Lasarte M, Lassus J, et al. Adrenomedullin: a marker of impaired hemodynamics, organ dysfunction, and poor prognosis in cardiogenic shock. Ann Intensive Care. 2017;7(1):1-10. DOI:10.1186/s13613-016-0229-2
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24. Pandhi P, Ter Maaten JM, Emmens JE, et al. Clinical value of pre-discharge bio-adrenomedullin as a marker of residual congestion and high risk of heart failure hospital readmission. Eur J Heart Fail. 2020;22(4):683-91. DOI:10.1002/ejhf.1693
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26. Morbach C, Marx A, Kaspar M, et al. Prognostic potential of midregional pro-adrenomedullin following decompensation for systolic heart failure: comparison with cardiac natriuretic peptides. Eur J Heart Fail. 2017;19(9):1166-75. DOI:10.1002/ejhf.859
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31. Nakamura R, Kato J, Kitamura K, et al. Adrenomedullin administration immediately after myocardial infarction ameliorates progression of heart failure in rats. Circulation. 2004;110(4):426-31. DOI:10.1161/01.CIR.0000136085.34185.83
32. Niu P, Shindo T, Iwata H, et al. Protective effects of endogenous adrenomedullin on cardiac hypertrophy, fibrosis, and renal damage. Circulation. 2004;109(14):1789-94. DOI:10.1161/01.CIR.0000118466.47982.CC
33. Looi YH, Kane KA, McPhaden AR, Wainwright CL. Adrenomedullin acts via nitric oxide and peroxynitrite to protect against myocardial ischaemia-induced arrhythmias in anaesthetized rats. Br J Pharmacol. 2006;148(5):599-609. DOI:10.1038/sj.bjp.0706771
34. Yoshizawa T, Takizawa S, Shimada S, et al. Effects of adrenomedullin on doxorubicin-induced cardiac damage in mice. Biol Pharm Bull. 2016;39(5):737-46.
DOI:10.1248/bpb.b15-00832
35. Li LL, Peng C, Zhang M, et al. Mesenchymal stem cells overexpressing adrenomedullin improve heart function through antifibrotic action in rats experiencing heart failure. Mol Med Rep. 2018;17(1):1437-44. DOI:10.3892/mmr.2017.8049
36. Nishikimi T, Karasawa T, Inaba C, et al. Effects of Long-Term Intravenous Administration of Adrenomedullin (AM) Plus hANP Therapy in Acute Decompensated Heart Failure A Pilot Study. Circ J. 2009;73(5):892-8. DOI:10.1253/circj.cj-08-0487
37. Nagaya N, Satoh T, Nishikimi T, et al. Hemodynamic, renal, and hormonal effects of adrenomedullin infusion in patients with congestive heart failure. Circulation. 2000;101(5):498-503. DOI:10.1161/01.cir.101.5.498
38. Geven C, Bergmann A, Kox M, Pickkers P. Vascular effects of adrenomedullin and the anti-adrenomedullin antibody adrecizumab in sepsis. Shock. 2018;50(2):132-40. DOI:10.1097/SHK.0000000000001103
39. Geven C, van Lier D, Blet A, et al. Safety, tolerability and pharmacokinetics/pharmacodynamics of the adrenomedullin antibody adrecizumab in a first-in-human study and during experimental human endotoxaemia in healthy subjects. Br J Clin Pharmacol. 2018;84(9):2129‑41. DOI:10.1111/bcp.13655

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1. Tsao CW, Lyass A, Enserro D, et al. Temporal trends in the incidence of and mortality associated with heart failure with preserved and reduced ejection fraction. JACC Heart Fail. 2018;6(8):678-85. DOI:10.1016/j.jchf.2018.03.006
2. Fomin IV. Chronic heart failure in Russian Federation: what do we know and what to do. Russian Journal of Cardiology. 2016;8:7-13 (in Russian).
DOI:10.15829/1560-4071-2016-8-7-13
3. Maggioni AP, Dahlström U, Filippatos G, et al. EURObservational Research Programme: regional differences and 1-year follow-up results of the Heart Failure Pilot Survey (ESC-HF Pilot). Eur J Heart Fail. 2013;15(7):808‑17. DOI:10.1093/eurjhf/hft050
4. Meijers WC, de Boer RA. Common risk factors for heart failure and cancer. Cardiovasc Res. 2019;115(5):844-53. DOI:10.1093/cvr/cvz035
5. Alieva AM, Pinchuk TV, Almazova II, et al. The clinical significance of determining the ST2 blood biomarker in patients with chronic heart failure. Consilium Medicum. 2021;23(6):522-6 (in Russian). DOI:10.26442/20751753.2021.6.200606
6. Alieva AM, Reznik EV, Hasanova ET, et al. Clinical value of blood biomarkers in patients with chronic heart failure. The Russian Archives of Internal Medicine. 2018;8(5):333-45 (in Russian). DOI:10.20514/2226-6704-2018-8-5-333-345
7. Kitamura K, Kangawa K, Kawamoto M, et al. Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem Biophys Res Commun. 1993;192(2):553-60. DOI:10.1006/bbrc.1993.1451
8. Ishimitsu T, Kojima M, Kangawa K, et al. Genomic structure of human adrenomedullin gene. Biochem Biophys Res Commun. 1994;203(1):631-9. DOI:10.1006/bbrc.1994.2229
9. Betowski J, Jamroz A. Adrenomedullin – what do we know 10 years since its discovery? Pol J Pharmacol. 2004;56:5-27.
10. Patel P, Mishra A, Sheikh AA, et al. Adrenomedullin: a novel peptide hormone. A review. J Pharmacogn Phytochem. 2017;6(6):2068-73.
11. Voors AA, Kremer D, Geven C, et al. Adrenomedullin in heart failure: pathophysiology and therapeutic application. Eur J Heart Fail. 2019;21(2):163-71. DOI:10.1002/ejhf.1366
12. Schönauer R, Els-Heindl S, Beck-Sickinger AG. Adrenomedullin – new perspectives of a potent peptide hormone. J Pept Sci. 2017;23(7-8):472-85. DOI:10.1002/psc.2953
13. Dschietzig T, Azad HA, Asswad L, et al. The adrenomedullin receptor acts as clearance receptor in pulmonary circulation. Biochem Biophys Res Commun. 2002;294(2):315-8. DOI:10.1016/S0006-291X(02)00474-6
14. Holmes D, Corr M, Thomas G, et al. Protective effects of intermedin/adrenomedullin-2 in a cellular model of human pulmonary arterial hypertension. Peptides. 2020;126:170267. DOI:10.1016/j.peptides.2020.170267
15. Jougasaki M, Wei CM, McKinley LJ, Burnett JC Jr. Elevation of circulating and ventricular adrenomedullin in human congestive heart failure. Circulation. 1995;92(3):286-9. DOI:10.1161/01.cir.92.3.286
16. Nishikimi T, Nakagawa Y. Adrenomedullin as a biomarker of heart failure. Heart Fail Clin. 2018;14(1):49-55. DOI:10.1016/j.hfc.2017.08.006
17. Piek A, Du W, de Boer RA, Silljé HHW. Novel heart failure biomarkers: why do we fail to exploit their potential? Crit Rev Clin Lab Sci. 2018;55(4):246-63. DOI:10.1080/10408363.2018.1460576
18. Gegenhuber A, Struck J, Dieplinger B, et al. Comparative evaluation of B-type natriuretic peptide, mid-regional pro-A-type natriuretic peptide, mid-regional pro-adrenomedullin, and Copeptin to predict 1-year mortality in patients with acute destabilized heart failure. J Card Fail. 2007;13(1):42-9. DOI:10.1016/j.cardfail.2006.09.004
19. Maisel A, Mueller C, Nowak R, et al. Mid-region pro-hormone markers for diagnosis and prognosis in acute dyspnea: results from the BACH (Biomarkers in Acute Heart Failure) trial. J Am Coll Cardiol. 2010;19:2062‑76. DOI:10.1016/j.jacc.2010.02.025
20. Weber J, Sachse J, Bergmann S, et al. Sandwich immunoassay for bioactive plasma adrenomedullin. J Appl Lab Med. 2017;2(2):222-33. DOI:10.1373/jalm.2017.023655
21. Self WH, Storrow AB, Hartmann O, et al. Plasma bioactive adrenomedullin as a prognostic biomarker in acute heart failure. Am J Emerg Med. 2016;34(2):257-62. DOI:10.1016/j.ajem.2015.10.033
22. Tolppanen H, Rivas-Lasarte M, Lassus J, et al. Adrenomedullin: a marker of impaired hemodynamics, organ dysfunction, and poor prognosis in cardiogenic shock. Ann Intensive Care. 2017;7(1):1-10. DOI:10.1186/s13613-016-0229-2
23. Ter Maaten JM, Kremer D, Demissei BG, et al. Bio-adrenomedullin as a marker of congestion in patients with new-onset and worsening heart failure. Eur J Heart Fail. 2019;21(6):732-43. DOI:10.1002/ejhf.1437
24. Pandhi P, Ter Maaten JM, Emmens JE, et al. Clinical value of pre-discharge bio-adrenomedullin as a marker of residual congestion and high risk of heart failure hospital readmission. Eur J Heart Fail. 2020;22(4):683-91. DOI:10.1002/ejhf.1693
25. Myasoedova EI. The level of proadrenomedullin in chronic heart failure of ischemic genesis: associations with clinical manifestations. Bulletin of Siberian Medicine. 2019;18(3):81-9 (in Russian). DOI:10.20538/1682-0363-2019-3-81-89
26. Morbach C, Marx A, Kaspar M, et al. Prognostic potential of midregional pro-adrenomedullin following decompensation for systolic heart failure: comparison with cardiac natriuretic peptides. Eur J Heart Fail. 2017;19(9):1166-75. DOI:10.1002/ejhf.859
27. Popov DA, Khrustalev AA. Prognostic value of new biomarkers in newborns and children with congenital heart disease. Laboratory service. 2019;8(4):13-21 (in Russian). DOI:10.17116/labs2019804113
28. Niu P, Shindo T, Iwata H, et al. Accelerated cardiac hypertrophy and renal damage induced by angiotensin II in adrenomedullin knockout mice. Hypertens Res. 2003;26(9):731-6. DOI:10.1291/hypres.26.731
29. Nishikimi T, Yoshihara F, Horinaka S, et al. Chronic administration of adrenomedullin attenuates transition from left ventricular hypertrophy to heart failure in rats. Hypertension. 2003;42(5):1034-41. DOI:10.1161/01.HYP.0000097604.64716.D2
30. Okumura H, Nagaya N, Itoh T, et al. Adrenomedullin infusion attenuates myocardial ischemia/reperfusion injury through the phosphatidylinositol 3-kinase/Akt-dependent pathway. Circulation. 2004;109(2):242-8. DOI:10.1161/01.CIR.0000109214.30211.7C
31. Nakamura R, Kato J, Kitamura K, et al. Adrenomedullin administration immediately after myocardial infarction ameliorates progression of heart failure in rats. Circulation. 2004;110(4):426-31. DOI:10.1161/01.CIR.0000136085.34185.83
32. Niu P, Shindo T, Iwata H, et al. Protective effects of endogenous adrenomedullin on cardiac hypertrophy, fibrosis, and renal damage. Circulation. 2004;109(14):1789-94. DOI:10.1161/01.CIR.0000118466.47982.CC
33. Looi YH, Kane KA, McPhaden AR, Wainwright CL. Adrenomedullin acts via nitric oxide and peroxynitrite to protect against myocardial ischaemia-induced arrhythmias in anaesthetized rats. Br J Pharmacol. 2006;148(5):599-609. DOI:10.1038/sj.bjp.0706771
34. Yoshizawa T, Takizawa S, Shimada S, et al. Effects of adrenomedullin on doxorubicin-induced cardiac damage in mice. Biol Pharm Bull. 2016;39(5):737-46.
DOI:10.1248/bpb.b15-00832
35. Li LL, Peng C, Zhang M, et al. Mesenchymal stem cells overexpressing adrenomedullin improve heart function through antifibrotic action in rats experiencing heart failure. Mol Med Rep. 2018;17(1):1437-44. DOI:10.3892/mmr.2017.8049
36. Nishikimi T, Karasawa T, Inaba C, et al. Effects of Long-Term Intravenous Administration of Adrenomedullin (AM) Plus hANP Therapy in Acute Decompensated Heart Failure A Pilot Study. Circ J. 2009;73(5):892-8. DOI:10.1253/circj.cj-08-0487
37. Nagaya N, Satoh T, Nishikimi T, et al. Hemodynamic, renal, and hormonal effects of adrenomedullin infusion in patients with congestive heart failure. Circulation. 2000;101(5):498-503. DOI:10.1161/01.cir.101.5.498
38. Geven C, Bergmann A, Kox M, Pickkers P. Vascular effects of adrenomedullin and the anti-adrenomedullin antibody adrecizumab in sepsis. Shock. 2018;50(2):132-40. DOI:10.1097/SHK.0000000000001103
39. Geven C, van Lier D, Blet A, et al. Safety, tolerability and pharmacokinetics/pharmacodynamics of the adrenomedullin antibody adrecizumab in a first-in-human study and during experimental human endotoxaemia in healthy subjects. Br J Clin Pharmacol. 2018;84(9):2129‑41. DOI:10.1111/bcp.13655

Авторы

А.М. Алиева*1, Н.В. Теплова1, К.В. Воронкова1, Т.В. Пинчук1, Р.К. Валиев2, Л.М. Шнахова3, А.М. Рахаев4, И.Г. Никитин1

1 ФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Москва, Россия;
2 ГБУЗ «Московский клинический научно-практический центр им. А.С. Логинова» Департамента здравоохранения г. Москвы, Москва, Россия;
3 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия;
4 ФКУ «Главное бюро медико-социальной экспертизы по Кабардино-Балкарской Республике» Минтруда и социальной защиты России, Нальчик, Россия
*amisha_alieva@mail.ru

________________________________________________

Amina M. Alieva*1, Natalia V. Teplova1, Kira V. Voronkova1, Tatyana V. Pinchuk1, Ramiz K. Valiev2, Lidia M. Shnakhova3, Alik M. Rahaev4, Igor G. Nikitin1

1 Pirogov Russian National Research Medical University, Moscow, Russia;
2 Loginov Moscow Clinical Scientific Center, Moscow, Russia;
3 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia;
4 Main Bureau of Medical and Social Expertise in the Kabardino-Balkarian Republic, Nalchik, Russia
*amisha_alieva@mail.ru

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